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Fibrin for Encapsulation of Human Mesenchymal Stem Cells for Chondrogenic Differentiation

  • Tamer A. E. Ahmed
  • Maxwell T. Hincke
Chapter
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 10)

Abstract

Age-related wear and tear of cartilage (osteoarthritis) and traumatic cartilage damage are a leading cause of disability in developed nations. Articular (hyaline) cartilage covers the ends of the bones of synovial joints and is a complex, multilayered structure varying in composition with location in a joint, and in relation to load and shear forces at that specific site. When damaged, articular cartilage tissue does not have the ability to repair itself, but rather is usually replaced by fibrocartilage which does not have suitable compressive properties, leading to breakdown, pain and can ultimately require replacement by prosthetic joint. Thus, cartilage repair remains a clinical challenge and few current treatments yield satisfactory clinical results over the long term. Regenerative medicine, using tissue engineering-based constructs to enhance cartilage repair by mobilizing chondrogenic cells, is a promising approach for restoration of structure and function, and provides a scientific basis for integrating the proper cell populations, suitable cellular signals and appropriate scaffolds for optimum tissue development and organ replacement strategies. Fibrin has been used as both a delivery vehicle and as a scaffolding matrix for tissue engineering. The emergence of mesenchymal stem cells (MSCs) as an important tool in regenerative medicine is due to their capability to repopulate and differentiate into several tissue lineages, including both cartilage and bone. Human MSCs have been used in combination with a wide range of fibrin scaffolds including both autologous and allogeneic human fibrin glue either as a platelet-rich or normal formulation, in addition to commercially available bovine fibrin hydrogel precursors. This approach permits high density of cells to be implanted, wherein chemical manipulation of the fibrin scaffold modulates its stability, strength and complement of growth factors, while maintaining the promise of an autologous repair solution. This review focuses on recent advances in the application of the fibrinogen/fibrin system for tissue engineering of articular cartilage.

Keywords

Mesenchymal Stem Cell Fibrin Glue Tranexamic Acid Chondrogenic Differentiation Cartilaginous Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Ahmed TA, Hincke MT (2010) Strategies for articular cartilage lesion repair and functional restoration. Tissue Eng Part B Rev 16:305–329PubMedCrossRefGoogle Scholar
  2. Ahmed TA, Griffith M, Hincke M (2007) Characterization and inhibition of fibrin hydrogel-degrading enzymes during development of tissue engineering scaffolds. Tissue Eng 13:1469–1477PubMedCrossRefGoogle Scholar
  3. Ahmed TA, Dare EV, Hincke M (2008) Fibrin: a versatile scaffold for tissue engineering applications. Tissue Eng Part B Rev 14:199–215PubMedCrossRefGoogle Scholar
  4. Ahmed TAE, Halpenny M, Atkins H, Giulivi A, Dervin G, Griffith M, Hincke M (2010) Stabilization of fibrin-mesenchymal stem cells (MSCs) constructs under hypoxic conditions during tissue engineering of articular cartilage. J Bone Joint Surg Br 92-B:2–3Google Scholar
  5. Ahmed TA, Giulivi A, Griffith M, Hincke M (2011) Fibrin glues in combination with mesenchymal stem cells to develop a tissue-engineered cartilage substitute. Tissue Eng Part A 17:323–335PubMedCrossRefGoogle Scholar
  6. Arita NA, Pelaez D, Cheung HS (2011) Activation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) is needed for the TGFbeta-induced chondrogenic and osteogenic differentiation of mesenchymal stem cells. Biochem Biophys Res Commun 405:564–569PubMedCrossRefGoogle Scholar
  7. Baumgartner L, Arnhold S, Brixius K, Addicks K, Bloch W (2010) Human mesenchymal stem cells: influence of oxygen pressure on proliferation and chondrogenic differentiation in fibrin glue in vitro. J Biomed Mater Res A 93:930–940PubMedGoogle Scholar
  8. Chen CC, Liao CH, Wang YH, Hsu YM, Huang SH, Chang CH, Fang HW (2012) Cartilage fragments from osteoarthritic knee promote chondrogenesis of mesenchymal stem cells without exogenous growth factor induction. J Orthop Res 30:393–400PubMedCrossRefGoogle Scholar
  9. Dickhut A, Dexheimer V, Martin K, Lauinger R, Heisel C, Richter W (2010) Chondrogenesis of human mesenchymal stem cells by local transforming growth factor-beta delivery in a biphasic resorbable carrier. Tissue Eng Part A 16:453–464PubMedCrossRefGoogle Scholar
  10. Diederichs S, Baral K, Tanner M, Richter W (2012) Interplay between local versus soluble TGF-beta and fibrin scaffolds: role of cells and impact on human mesenchymal stem cell chondrogenesis. Tissue Eng Part A 18:1140–1150PubMedCrossRefGoogle Scholar
  11. Haleem AM, Singergy AA, Sabry D, Atta HM, Rashed LA, Chu CR, El Shewy MT, Azzam A, Abdel Aziz MT (2010) The clinical use of human culture-expanded autologous bone marrow mesenchymal stem cells transplanted on platelet-rich fibrin glue in the treatment of articular cartilage defects: a pilot study and preliminary results. Cartilage 1:253–261PubMedCrossRefGoogle Scholar
  12. Ho ST, Cool SM, Hui JH, Hutmacher DW (2010) The influence of fibrin based hydrogels on the chondrogenic differentiation of human bone marrow stromal cells. Biomaterials 31:38–47PubMedCrossRefGoogle Scholar
  13. Im GI, Shin YW, Lee KB (2005) Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? Osteoarthritis Cartilage 13:845–853PubMedCrossRefGoogle Scholar
  14. Jung SN, Rhie JW, Kwon H, Jun YJ, Seo JW, Yoo G, Oh DY, Ahn ST, Woo J, Oh J (2010) In vivo cartilage formation using chondrogenic-differentiated human adipose-derived mesenchymal stem cells mixed with fibrin glue. J Craniofac Surg 21:468–472PubMedCrossRefGoogle Scholar
  15. Kessler MW, Grande DA (2008) Tissue engineering and cartilage. Organogenesis 4:28–32PubMedCrossRefGoogle Scholar
  16. Kupcsik L, Alini M, Stoddart MJ (2009) Epsilon-aminocaproic acid is a useful fibrin degradation inhibitor for cartilage tissue engineering. Tissue Eng Part A 15:2309–2313PubMedCrossRefGoogle Scholar
  17. Lee HH, Haleem AM, Yao V, Li J, Xiao X, Chu CR (2011) Release of bioactive adeno-associated virus from fibrin scaffolds: effects of fibrin glue concentrations. Tissue Eng Part A 17:1969–1978PubMedCrossRefGoogle Scholar
  18. Li Z, Kupcsik L, Yao SJ, Alini M, Stoddart MJ (2009) Chondrogenesis of human bone marrow mesenchymal stem cells in fibrin-polyurethane composites. Tissue Eng Part A 15:1729–1737PubMedCrossRefGoogle Scholar
  19. Li Z, Kupcsik L, Yao SJ, Alini M, Stoddart MJ (2010a) Mechanical load modulates chondrogenesis of human mesenchymal stem cells through the TGF-beta pathway. J Cell Mol Med 14:1338–1346PubMedCrossRefGoogle Scholar
  20. Li Z, Yao SJ, Alini M, Stoddart MJ (2010b) Chondrogenesis of human bone marrow mesenchymal stem cells in fibrin-polyurethane composites is modulated by frequency and amplitude of dynamic compression and shear stress. Tissue Eng Part A 16:575–584PubMedCrossRefGoogle Scholar
  21. Park JS, Yang HN, Woo DG, Jeon SY, Park KH (2011a) Chondrogenesis of human mesenchymal stem cells in fibrin constructs evaluated in vitro and in nude mouse and rabbit defects models. Biomaterials 32:1495–1507PubMedCrossRefGoogle Scholar
  22. Park JS, Shim MS, Shim SH, Yang HN, Jeon SY, Woo DG, Lee DR, Yoon TK, Park KH (2011b) Chondrogenic potential of stem cells derived from amniotic fluid, adipose tissue, or bone marrow encapsulated in fibrin gels containing TGF-beta3. Biomaterials 32:8139–8849PubMedCrossRefGoogle Scholar
  23. Pelaez D, Huang CY, Cheung HS (2009) Cyclic compression maintains viability and induces chondrogenesis of human mesenchymal stem cells in fibrin gel scaffolds. Stem Cells Dev 18:93–102PubMedCrossRefGoogle Scholar
  24. Pelaez D, Arita N, Cheung HS (2012) Extracellular signal-regulated kinase (ERK) dictates osteogenic and/or chondrogenic lineage commitment of mesenchymal stem cells under dynamic compression. Biochem Biophys Res Commun 417:1286–1291PubMedCrossRefGoogle Scholar
  25. Schatti O, Grad S, Goldhahn J, Salzmann G, Li Z, Alini M, Stoddart MJ (2011) A combination of shear and dynamic compression leads to mechanically induced chondrogenesis of human mesenchymal stem cells. Eur Cell Mater 22:214–225PubMedGoogle Scholar
  26. Yang HN, Park JS, Woo DG, Jeon SY, Do HJ, Lim HY, Kim SW, Kim JH, Park KH (2011) Chondrogenesis of mesenchymal stem cells and dedifferentiated chondrocytes by transfection with SOX Trio genes. Biomaterials 32:7695–7704PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Medical Biotechnology DepartmentGenetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications (SRTA City)AlexandriaEgypt
  2. 2.Division of Clinical and Functional Anatomy, Cellular & Molecular MedicineUniversity of OttawaOttawaCanada

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